Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/36128—Control systems
  • A61N1/36135—Control systems using physiological parameters
  • A61N1/36139—Control systems using physiological parameters with automatic adjustment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
  • A61N1/0551—Spinal or peripheral nerve electrodes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
  • A61N1/36114—Cardiac control, e.g. by vagal stimulation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
  • A61N1/36114—Cardiac control, e.g. by vagal stimulation
  • A61N1/36117—Cardiac control, e.g. by vagal stimulation for treating hypertension

Definitions

• the sensor is adapted to sense at least one physiological parameter indicative of an evoked response to the neural stimulation therapy.
• the response extractor is configured to receive a time series of parameter data from the sensor and to extract evoked response data from the time series of parameter data and configured to determine if the evoked response data substantially returns to the baseline between neural stimulation bursts.
• FIG. 15 illustrates a neural stimulator device embodiment adapted to deliver intermittent neural stimulation therapy, according to various embodiments.
• the automatic nervous system regulates "involuntary" organs, while the contraction of voluntary (skeletal) muscles is controlled by somatic motor nerves.
• involuntary organs include respiratory and digestive organs, and also include blood vessels and the heart.
• the ANS functions in an involuntary, reflexive manner to regulate glands, to regulate muscles in the skin, eye, stomach, intestines and bladder, and to regulate cardiac muscle and the muscle around blood vessels, for example.
• the ANS includes the sympathetic nervous system and the parasympathetic nervous system.
• the sympathetic nervous system is affiliated with stress and the "fight or flight response" to emergencies. Among other effects, the "fight or flight response” increases blood pressure and heart rate to increase skeletal muscle blood flow, and decreases digestion to provide the energy for "fighting or fleeing.”
• the parasympathetic nervous system is affiliated with relaxation and the "rest and digest response” which, among other effects, decreases blood pressure and heart rate, and increases digestion to conserve energy.
• the ANS maintains normal internal function and works with the somatic nervous system.
• Stimulating the parasympathetic nervous system constricts the pupil, increases saliva and mucus production, contracts the bronchial muscle, increases secretions and motility in the stomach and large intestine, increases digestion in the small intestine, increases urine secretion, and contracts the wall and relaxes the sphincter of the bladder.
• the functions associated with the sympathetic and parasympathetic nervous systems are many and can be complexly integrated with each other.
• FIGS. 6A-6C illustrate various embodiments for monitoring a response to an intermittent NS burst. Multiple bursts can be analyzed, according to various embodiments. Each figure illustrates one neural stimulation burst among a plurality of INS stimulation bursts of a programmed NS therapy.
• the NS burst includes a plurality of NS pulses that are preceded and followed by a time without NS pulses.
• an ANS signal is monitored over time and marked with the NS event, which is a time point with a fixed offset from the start of the NS burst.
• n of a fixed duration (the duration being set according to expectations about how long the transitory response will last).
• the cross- correlation between corresponding intervals after different NS events [e.g., E(l,z), E(2,z), ... E(N,i)] are expected to be highly correlated for intervals during which there is in fact an NS-generated signal response, and are expected to be uncorrected when intervals are compared that occur after the NS response has diminished to background levels.
• the last interval exhibiting significant correlation would be the end of the transient response.
• the signals could be pre- filtered or averaged to remove non-stationary fluctuations before correlation, for example, to remove slow frequency drifts in signal levels.
• Different stimulation locations may be varied to change the axon (neural pathway) sets that are captured, to allow search over different neural pathways for an optimal transient response.
• the present subject matter is designed to allow NS to be configured to achieve long-term clinical treatment effects (outcomes) while avoiding or otherwise controlling specific transient response effects.
• the NS treatment effects (outcomes) can be measured by standard clinical indicators of disease state.
• Measures of a clinical response are distinct from measures of a NS evoked response, which various embodiments described herein actively manage to be transient.
• Some embodiments for generating and improving or optimizing a response select the stimulation parameters dependent on the baseline HR or baseline BP or other baseline physiological measure. For example, if baseline HR is high, neural targets are selected to increase parasympathetic tone to decrease HR and provide a desired direct and or indirect HR response. If baseline HR is low, neural targets are selected to increase sympathetic tone to increase HR and provide a desired direct or indirect HR response.
• Some embodiments deliver NS while controlling the evoked response of HR or BP (or other physiological variable) to be below a threshold level. For example, this permits NS to be delivered while ensuring there is no change or only an acceptably low change in HR, BP or other monitored physiological parameter that is subject to transient response control.
• a therapeutically effective NS level can be determined by detecting specific evoked responses known to be associated with an effective level of stimulation. For example, vagal stimulation configured to evoke laryngeal vibration may indicate a minimum effective therapeutic level (i.e.
• Electrical neural stimulation is used in this document as an example of neural stimulation.
• electrical stimulation for example, a train of neural stimulation pulses (current or voltage) can be delivered during a duty cycle of stimulation.
• Stimulation pulse waveforms can be square pulses or other morphologies.
• HR sensors can be used to record HR time series signals
• BP sensors can be used to record BP time series signals.
• a neural stimulation (NS) event e.g., an intermittent burst of given amplitude, duration, location, polarity, etc.
• NS neural stimulation
• Time series decomposition can extract the evoked response that is correlated with intermittent NS events of a given dose.
• the duration of the evoked response can be determined by determining the length of time the correlated perturbations due to a NS event persist.
• E A [t] — E[S, t] where E AVG is the averaged response time series.
• FIG. 15 illustrates a neural stimulator device embodiment adapted to deliver intermittent neural stimulation therapy, according to various embodiments.
• the illustrated device 1535 can be an implantable device or an external device.
• the illustrated device includes a neural stimulation delivery system 1536 adapted to deliver a neural stimulation signal to the neural stimulation electrode(s) or transducer(s) 1537 to deliver the neural stimulation therapy.
• Examples of neural stimulation electrodes include nerve cuff electrodes, intravascularly placed electrodes, and transcutaneous electrodes.
• Examples of neural stimulation transducers include ultrasound, light and magnetic energy transducers.
• Some embodiments deliver neural stimulation without monitoring the direct response to the stimulation. For example, some embodiments may deliver stimulation without attempting to drive a specific change in heart rate for each stimulation burst, and only limit the change to be transient.
• the pulse generator for each channel outputs a train of neural stimulation pulses which may be varied by the controller as to amplitude, frequency, duty-cycle, and the like.
• each of the neural stimulation channels uses a lead which can be intravascularly disposed near an appropriate neural target. Other types of leads and/or electrodes may also be employed.
• a nerve cuff electrode may be used in place of an intravascularly disposed electrode to provide neural stimulation.
• the leads of the neural stimulation electrodes are replaced by wireless links.
• the figure illustrates a telemetry interface 1775 connected to the microprocessor, which can be used to communicate with an external device.
• the illustrated microprocessor 1759 is capable of performing neural stimulation therapy routines and myocardial (CRM) stimulation routines.
• NS therapy routines include, but are not limited to, therapies to provide physical conditioning and therapies to treat ventricular remodeling, hypertension, sleep disordered breathing, blood pressure control such as to treat hypertension, cardiac rhythm management, myocardial infarction and ischemia, heart failure, epilepsy, depression, for pain, migraines, eating disorders and obesity, and movement disorders.
• the present subject matter is not limited to a particular neural stimulation therapy.
• FIG. 18 illustrates a system 1876 including an implantable medical device (IMD) 1877 and an external system or device 1878, according to various embodiments of the present subject matter.
• IMD implantable medical device
• Various embodiments of the IMD include NS functions or include a combination of NS and CRM functions.
• the IMD may also deliver biological agents and pharmaceutical agents.
• the external system and the IMD are capable of wirelessly communicating data and instructions.
• the external system and IMD use telemetry coils to wirelessly communicate data and instructions.
• the programmer can be used to adjust the programmed therapy provided by the IMD, and the IMD can report device data (such as battery and lead resistance) and therapy data (such as sense and stimulation data) to the programmer using radio telemetry, for example.
• device data such as battery and lead resistance
• therapy data such as sense and stimulation data
• the illustrated NS device and the CRM device are capable of wirelessly communicating with each other, and the external system is capable of wirelessly communicating with at least one of the NS and the CRM devices.
• various embodiments use telemetry coils to wirelessly communicate data and instructions to each other.
• communication of data and/or energy is by ultrasonic means.
• various embodiments provide a communication cable or wire, such as an intravenously-fed lead, for use to communicate between the NS device and the CRM device.
• the external system functions as a communication bridge between the NS and CRM devices.
• the illustrated system includes leadless ECG electrodes 2083 on the housing of the device. These ECG electrodes are capable of being used to detect heart rate, for example.
• Baroreflex neural targets can be found in the wall of the auricles of the heart, cardiac fat pads, vena cava, aortic arch and carotid sinus.
• Examples of afferent nerve trunks that can serve as baroreflex neural targets include the vagus, aortic and carotid nerves.
• Stimulating baroreceptors inhibits sympathetic nerve activity (stimulates the parasympathetic nervous system) and reduces systemic arterial pressure by decreasing peripheral vascular resistance and cardiac contractility. Baroreceptors are naturally stimulated by internal pressure and the stretching of the arterial wall.
• Chemoreceptors which are sensory nerve cells that respond to chemical stimuli, may be stimulated to stimulate a desired autonomic reflex response.

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• 2011
  • 2011-04-14 US US13/086,806 patent/US9126044B2/en active Active
  • 2011-04-14 JP JP2013505131A patent/JP5624672B2/ja not_active Expired - Fee Related
  • 2011-04-14 WO PCT/US2011/032450 patent/WO2011130488A2/en active Application Filing
  • 2011-04-14 AU AU2011239668A patent/AU2011239668B2/en not_active Ceased
  • 2011-04-14 EP EP11716739.5A patent/EP2558160B1/en active Active
• 2015
  • 2015-09-01 US US14/842,154 patent/US9504833B2/en active Active
• 2016
  • 2016-06-02 US US15/171,526 patent/US9782591B2/en active Active
• 2017
  • 2017-07-26 US US15/660,384 patent/US10668287B2/en active Active
• 2020
  • 2020-05-06 US US16/868,229 patent/US20200261728A1/en not_active Abandoned

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